Prevention of Stirring-Induced Microparticle Formation in Monoclonal Antibody Solutions

Monoclonal antibodies are being widely used for the treatment of various diseases. Microparticle formation in high-concentration protein solutions is a major problem during the manufacture of therapeutic monoclonal antibodies, because aggregation leads to fouling of aseptic filters and may lead to a...

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Bibliographic Details
Published in:	Biological & Pharmaceutical Bulletin Vol. 33; no. 6; pp. 1043 - 1046
Main Authors:	Ishikawa, Tomoyoshi, Kobayashi, Noritaka, Osawa, Chie, Sawa, Eiji, Wakamatsu, Kaori
Format:	Journal Article
Language:	English
Published:	Japan The Pharmaceutical Society of Japan 2010 Pharmaceutical Society of Japan Japan Science and Technology Agency
Subjects:	aggregation Antibodies, Monoclonal - chemistry Chemistry, Pharmaceutical - instrumentation Chemistry, Pharmaceutical - methods Filtration Humans microparticle monoclonal antibody Particle Size Pharmaceutical Solutions - chemistry shear stress stirring Stress, Mechanical
Online Access:	Get full text
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Summary:	Monoclonal antibodies are being widely used for the treatment of various diseases. Microparticle formation in high-concentration protein solutions is a major problem during the manufacture of therapeutic monoclonal antibodies, because aggregation leads to fouling of aseptic filters and may lead to an immunogenic reaction in patients. We found that stirring using a traditional bottom-magnetic type stirrer results in extensive and sustained formation of 500-nm diameter protein microparticles arising from shear stress on protein molecules. The antibody solution stirred for only 5 min using this type of stirrer exhibited significant fouling of aseptic filter membranes. In contrast, a top-entering type stirrer did not lead to the formation of microparticles, and the solution did not exhibit membrane fouling even after 30 min of stirring. We conclude that a top-entering type stirrer is more suited for the manufacture of concentrated therapeutic monoclonal antibody solutions.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0918-6158 1347-5215
DOI:	10.1248/bpb.33.1043